PROJECT SUMMARY/ABSTRACT Tranexamic acid (TXA), a drug that stops bleeding, is the only drug treatment that improves survival in adults with serious bleeding after injuries. However, TXA has not been used routinely in children with traumatic bleeding because no studies have appropriately evaluated TXA for injured children. Such a study has the potential for significant impact in improving the lives of injured children and their families, if found to be successful. Our long-term objective is to evaluate the benefits and risks of TXA in severely injured children. We will achieve this by ultimately conducting two large-scale, multicenter, randomized controlled trials of TXA use in severely injured children. One trial will evaluate TXA in children with severe injuries to the body (?torso injuries?, i.e., to the abdomen and chest) and the second trial will evaluate TXA in children with moderate-to- severe traumatic brain injuries (TBIs). However, conducting a clinical trial in critically ill children is challenging due to lower disease frequency and complex parent consent/child assent procedures. We therefore propose here to conduct a pilot study, designed similarly to the full-scale trials but with much smaller patient enrollment, to assess the feasibility of, and fill crucial information gaps for the two subsequent large-scale clinical trials. We will randomize injured children to one of three study arms: two different TXA doses or placebo. The specific aim of the proposed pilot study is to demonstrate the ability to efficiently identify and enroll children with hemorrhagic torso injuries or TBIs into a multicenter, randomized controlled pilot study evaluating these two doses of TXA and placebo. We will enroll 40 children who meet inclusion and exclusion criteria at 4 participating sites. To demonstrate the ability to collect outcome measures, we will collect the identical anticipated outcome measures for the subsequent clinical trials: total blood products transfused over the initial 48 hours of care (torso injury trial), and intracranial hemorrhage progression in first 24 hours and neurocognitive function at 6 months after randomization (TBI trial). We will also collect safety outcomes, specifically venothromboembolic events (i.e., blot clots in the blood vessels) and seizures within the initial 24 hours of study drug. Additional objectives of this pilot study are to: evaluate the ability to efficiently screen, identify, consent, randomize, and initiate the study intervention within 3 hours of injury, assess protocol adherence and variability of care in enrolled patients, and identify operational efficiencies with the potential to enhance the success of the subsequent trials.